ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Detection of BRCA1, BRCA2, and ATM Alterations in Matched Tumor Tissue and Circulating Tumor DNA in Patients with Prostate Cancer Screened in PROfound.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 4 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 4 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Circulating Tumor DNA as a Biomarker for Precision Medicine in Prostate Cancer: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Germline and somatic testing for homologous repair deficiency in patients with prostate cancer (part 1 of 2).Prostate cancer and prostatic diseases · 2025Guideline
- The Impact of Uncommon HRR Alterations as Predictors of Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials.Targeted oncology · 2025Pooled it
- Efficacy and safety of PARP inhibitors in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis of clinical trials.Cancer treatment reviews · 2023Pooled it
- Detection of Homologous Recombination Repair Gene Mutations by Tumor Tissue and Circulating Tumor DNA Testing in Prostate Cancer in the Phase III PROpel Trial.JCO precision oncology · 2026Trial
- Urinary extracellular vesicle microRNA profiles and prostate cancer biopsy outcome: Moderate discrimination and quantified optimism under leakage-controlled machine learning.Biochemistry and biophysics reports · 2026Article
- Liquid biopsy: a new window on the BRCA genes.ESMO open · 2026Review
- Advancing the applications of liquid biopsies in oncology.Nature reviews. Genetics · 2026Review
- Real-World Outcomes of Olaparib in Japanese Patients With BRCA-Mutated Metastatic Castration-Resistant Prostate Cancer: Exploratory Analysis of BRCA2 Loss and Microsatellite Instability Status.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- Evolving role of biomarkers beyond prostate‑specific antigen in refining prostate cancer screening: From blood‑based tests to urinary and genetic markers (Review).Molecular medicine reports · 2026Review
- Prognostic value of circulating tumor DNA and copy-number alterations in patients receiving tandem [BMC cancer · 2026Observational
- Article
- Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer.Cancer metastasis reviews · 2026Review
- Prognostic implications of tissue-based homologous recombination deficiency in metastatic gastric cancer treated with immune checkpoint inhibitor plus chemotherapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Combined ctDNA and serum PSA for dynamic monitoring of metastatic prostate cancer starting first-line treatment: a prospective national cohort study.Nature cancer · 2026Article
- Circulating Tumor DNA as Emerging Predictive and Prognostic Biomarker in Prostate Cancer.Cancers · 2026Review
- Liquid Biopsy in Advanced Prostate Cancer.Cancers · 2026Review
- Camonsertib, an ATRi, in Combination with Low-Dose Gemcitabine in Solid Tumors with DNA Damage Response Aberrations: Preclinical and Phase Ib Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Homologous recombination repair and breast cancer gene testing in prostate cancer: expert perspectives and practical guidance on best practice from sample acquisition to biomarker-informed clinical decision-making.Frontiers in oncology · 2026Article
- Circulating tumour DNA in mCRPC: bridging tumour biology and real-time treatment monitoring.Frontiers in molecular medicine · 2026Review
Corrections and comments
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Authors and funding
18 authors at 11 institutions in 10 countries.
Funding
Abstract
purposeNot all patients with metastatic castration-resistant prostate cancer (mCRPC) have sufficient tumor tissue available for multigene molecular testing. Furthermore, samples may fail because of difficulties within the testing procedure. Optimization of screening techniques may reduce failure rates; however, a need remains for additional testing methods to detect cancers with alterations in homologous recombination repair genes. We evaluated the utility of plasma-derived circulating tumor DNA (ctDNA) in identifying deleterious BRCA1, BRCA2 (BRCA), and ATM alterations in screened patients with mCRPC from the phase III PROfound study. PATIENTS AND
methodsTumor tissue samples were sequenced prospectively at Foundation Medicine, Inc. (FMI) using an investigational next-generation sequencing (NGS) assay based on FoundationOne®CDx to inform trial eligibility. Matched ctDNA samples were retrospectively sequenced at FMI, using an investigational assay based on FoundationOne®Liquid CDx.
results81% (503/619) of ctDNA samples yielded an NGS result, of which 491 had a tumor tissue result. BRCA and ATM status in tissue compared with ctDNA showed 81% positive percentage agreement and 92% negative percentage agreement, using tissue as reference. At variant-subtype level, using tissue as reference, concordance was high for nonsense (93%), splice (87%), and frameshift (86%) alterations but lower for large rearrangements (63%) and homozygous deletions (27%), with low ctDNA fraction being a limiting factor.
conclusionsWe demonstrate that ctDNA can greatly complement tissue testing in identifying patients with mCRPC and BRCA or ATM alterations who are potentially suitable for receiving targeted PARP inhibitor treatments, particularly patients with no or insufficient tissue for genomic analyses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.